445 GENES AND MOLECULAR PATHWAYS COMMON TO THE RODENT MODEL OF UNILATERAL URETERAL OBSTRUCTION AND HUMAN URETEROPELVIC JUNCTION OBSTRUCTION

Abstract

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Kidney & Ureter1 Apr 2010445 GENES AND MOLECULAR PATHWAYS COMMON TO THE RODENT MODEL OF UNILATERAL URETERAL OBSTRUCTION AND HUMAN URETEROPELVIC JUNCTION OBSTRUCTION Hrair-George Mesrobian, Michael E. Mitchell, Brian D. Halligan, and Bassam T. Wakim Hrair-George MesrobianHrair-George Mesrobian More articles by this author , Michael E. MitchellMichael E. Mitchell More articles by this author , Brian D. HalliganBrian D. Halligan More articles by this author , and Bassam T. WakimBassam T. Wakim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.517AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The molecular response of the developing kidney to unilateral ureteral obstruction (UUO) has been extensively studied in the rodent model. The recent application of proteomic tools to discover differentially expressed proteins in the urine of infants with ureteropelvic junction obstruction (UPJO) represents a promising non invasive approach to the understanding of the pathophysiologic processes of the human disease. In this analysis, we compare literature derived molecules implicated in the pathophysiology of experimental UUO to up and down regulated molecules derived from human unilateral grade 4 UPJO urinary proteomic data. METHODS The dataset for the rodent model was derived from a review of the literature since 2000. The dataset for the human disease was derived from the whole urinary proteome analysis by LC-MS/MS of 70 specimens from infants with unilateral grade 4 UPJO and 36 age matched normal controls. The datasets were uploaded to Ingenuity Pathway Analysis (IPA;www.Ingenuity.com) and compared for common genes, functions and networks. RESULTS There were 186 entries in the experimental list, 132 entries in the 1-6 months and 90 in the 7-12 months UPJO age groups respectively. Only 6 originating from the experimental group are detected in the urine of infants with UPJO. These consist of beta 2 microglobulin, cartilage associated protein, epidermal growth factor, colony stimulating factor-1, N-acetylglucosaminidase and gamma-glutamyltransferase. However, there is funtional overlap between the groups resulting from the interaction with molecules with no change in their relative abundance (see table). CONCLUSIONS The experimental model of UUO may mimic the response to obstruction-not its cause-and caution is advised in extrapolating to human UPJO. Nevertheless, the discovery of 6 shared markers of obstruction in the urine of patients has important implications. These genes can be specifically targeted for research however, pathways and functions resulting from the interaction of additional molecules (neither up or down regulated) may need to be taken into consideration as well. Milwaukee, WI© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e176 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hrair-George Mesrobian More articles by this author Michael E. Mitchell More articles by this author Brian D. Halligan More articles by this author Bassam T. Wakim More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...